BACKGROUND: Extracellular sulfatases (Sulfs), sulfatase 1 (Sulf1) and sulfatase 2 (Sulf2), play a pivotal role in cell signaling by remodeling the 6-O-sulfation of heparan sulfate proteoglycans on the cell surface. The present study examined the effects of Sulfs on angiotensin II (Ang II)-induced hypertensive mediator expression and vascular smooth muscle cells (VSMCs) proliferation in spontaneously hypertensive rats (SHR). METHODS: Ang II receptors, 12-lipoxygenase (12-LO), and endothelin-1 (ET-1) messenger RNA (mRNA) expressions in SHR VSMCs were analyzed by real-time polymerase chain reaction and Western blotting. VSMCs proliferation was determined by [³ H]-thymidine incorporation. RESULTS: Basal Sulfs mRNAs expression and enzyme activity were elevated in SHR VSMCs. However, Sulfs had no effect on the basal or Ang II-induced 12-LO and ET-1 mRNA expression in SHR VSMCs. The inhibition of Ang II-induced 12-LO and ET-1 expression by blockade of the Ang II type 2 receptor (AT₂ R) pathway was not observed in Sulf1 siRNA-transfected SHR VSMCs. However, Sulf2 did not affect the action of AT₂ R inhibitor on Ang II-induced 12-LO and ET-1 expression in SHR VSMCs. The down-regulation of Sulf1 induced a reduction of AT₂ R mRNA expression in SHR VSMCs. In addition, the inhibition of Ang II-induced VSMCs proliferation by blockade of the AT₂ R pathway was mediated by Sulf1 in SHR VSMCs. CONCLUSION: These findings suggest that extracellular sulfatase Sulf1 plays a modulatory role in the AT₂ R pathway that leads to an Ang II-induced hypertensive effects in SHR VSMCs.
Angiotensin II* ; Angiotensins* ; Arachidonate 12-Lipoxygenase ; Blotting, Western ; Down-Regulation ; Endothelin-1 ; Heparan Sulfate Proteoglycans ; Hypertension ; Muscle, Smooth, Vascular* ; Rats, Inbred SHR* ; Real-Time Polymerase Chain Reaction ; Receptor, Angiotensin, Type 2* ; RNA, Messenger ; Sulfatases

BACKGROUND: Extracellular sulfatases (Sulfs), sulfatase 1 (Sulf1) and sulfatase 2 (Sulf2), play a pivotal role in cell signaling by remodeling the 6-O-sulfation of heparan sulfate proteoglycans on the cell surface. The present study examined the effects of Sulfs on angiotensin II (Ang II)-induced hypertensive mediator expression and vascular smooth muscle cells (VSMCs) proliferation in spontaneously hypertensive rats (SHR).METHODS: Ang II receptors, 12-lipoxygenase (12-LO), and endothelin-1 (ET-1) messenger RNA (mRNA) expressions in SHR VSMCs were analyzed by real-time polymerase chain reaction and Western blotting. VSMCs proliferation was determined by [³ H]-thymidine incorporation.RESULTS: Basal Sulfs mRNAs expression and enzyme activity were elevated in SHR VSMCs. However, Sulfs had no effect on the basal or Ang II-induced 12-LO and ET-1 mRNA expression in SHR VSMCs. The inhibition of Ang II-induced 12-LO and ET-1 expression by blockade of the Ang II type 2 receptor (AT₂ R) pathway was not observed in Sulf1 siRNA-transfected SHR VSMCs. However, Sulf2 did not affect the action of AT₂ R inhibitor on Ang II-induced 12-LO and ET-1 expression in SHR VSMCs. The down-regulation of Sulf1 induced a reduction of AT₂ R mRNA expression in SHR VSMCs. In addition, the inhibition of Ang II-induced VSMCs proliferation by blockade of the AT₂ R pathway was mediated by Sulf1 in SHR VSMCs.CONCLUSION: These findings suggest that extracellular sulfatase Sulf1 plays a modulatory role in the AT₂ R pathway that leads to an Ang II-induced hypertensive effects in SHR VSMCs.
Angiotensin II ; Angiotensins ; Arachidonate 12-Lipoxygenase ; Blotting, Western ; Down-Regulation ; Endothelin-1 ; Heparan Sulfate Proteoglycans ; Hypertension ; Muscle, Smooth, Vascular ; Rats, Inbred SHR ; Real-Time Polymerase Chain Reaction ; Receptor, Angiotensin, Type 2 ; RNA, Messenger ; Sulfatases

CCL5, a proinflammatory chemokine, has been shown to attenuate angiotensin (Ang) II-induced expression of hypertensive mediators as well as Ang II-induced inhibition of anti-hypertensive mediator expression in vascular smooth muscle cells (VSMCs) of spontaneously hypertensive rats (SHR). In the present study, functional roles of CCL5 on hypertension were examined in developing hypertension state SHR (DHSHR). DHSHR at an age of 8 weeks were injected CCL5 (1.5 microg/kg) subcutaneously twice a day for 3 weeks (SHRi, n=5). Control groups consisted of normal age-matched saline-treated SHR (SHRc, n=5) and normotensive Wistar-Kyoto rats (WKY, n=5). Effect of CCL5 on blood pressure was measured before treatment, weekly during treatment, and 1 day after the final injection. After injecting for 3 weeks, effects of CCL5 on expression of hypertensive mediators were examined in thoracic aorta tissues and VSMCs. Blood pressure in SHRi was maintained without any elevation during the treatment period, whereas blood pressure in SHRc progressively increased with age. Expression of Ang II subtype I receptor was reduced in SHRi thoracic aorta tissues and VSMCs compared to those in SHRc. In addition, expression levels of hypertensive mediators were significantly reduced in SHRi thoracic aorta tissues and VSMCs compared to those in SHRc. In contrast, AMP-activated protein kinase (AMPK) activity and interleukin-10 (IL-10) expression were elevated in SHRi thoracic aorta tissues and VSMCs compared to levels in SHRc. These results suggest that reduction of hypertensive mediators and elevation of anti-hypertensive mediators by CCL5 treatment promotes maintenance of blood pressure in DHSHR.
AMP-Activated Protein Kinases ; Angiotensins ; Animals ; Aorta, Thoracic ; Blood Pressure* ; Hypertension* ; Interleukin-10 ; Muscle, Smooth, Vascular ; Rats ; Rats, Inbred SHR*

BACKGROUND: Fentanyl, which is a potent synthetic micron-opioid receptor agonist, is one of the most widely used opioids in anesthesia and pain control. However, the pharmacodynamics of fentanyl show wide inter-individual variability. Therefore, this study was conducted to evaluate the influence of the blood-brain barrier transporter protein, p-glycoprotein, and micron-opioid receptor genetic polymorphism on fentanyl pharmacodynamics. METHODS: Seventy-nine patients who underwent posterior lumbar interbody fusion (PLIF) were included in this study. Postoperatively, the patients received fentanyl via an intravenous patient controlled analgesia device. The cumulative fentanyl doses and other pharmacodynamic data were then recorded at 2 h, 6 h, 12 h, 24 h and 48 h after the operation. In addition, genomic DNA was isolated from the patient's peripheral leukocytes and then evaluated for the presence of OPRM1 A118G and ABCB1 C3435T genetic polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The results of this study indicated that ABCB1 C3435T genetic polymorphism may be related to the cumulative fentanyl requirement for postoperative pain control. However, these findings were not statistically significant (P = 0.09). In addition, no relationship was observed between OPRM1 A118G and the cumulative postoperative fentanyl requirement. However, the cumulative postoperative fentanyl requirement was lower in the TTAA group (ABCB1 3435 TT, OPRM1 118 AA) than in the CCGG group (ABCB13435 CC, OPRM1 118 GG). CONCLUSIONS: The ABCB1 C3435T polymorphism may affect fentanyl pharmacodynamics. However, further studies are required to confirm the relationship between p-glycoprotein and fentanyl.
Analgesia, Patient-Controlled ; Analgesics, Opioid ; Anesthesia ; Blood-Brain Barrier ; DNA ; Fentanyl ; Humans ; Leukocytes ; P-Glycoprotein ; Pain, Postoperative ; Pharmacogenetics ; Polymorphism, Genetic

Background: There are inconsistent reports regarding the association between general anesthesia and adverse neurodevelopmental and behavioral disorders in children. Methods: This nationwide administrative cohort study included children born in Korea between 2008 and 2009, and followed until December 31, 2017. The cohort included 93,717 participants who received general anesthesia with endotracheal intubation (ETI) who were matched to unexposed subjects in a 1:1 ratio. General anesthesia was defined by National Health Insurance Service treatment codes with intratracheal anesthesia, and the index date was the first event of general anesthesia. The primary outcome was attention deficit hyperactive disorder (ADHD), which was defined as at least a principal diagnosis of 10th revision of the International Classification of Diseases code F90.X after the age of 72 months.Neurodevelopment, which was assessed using a developmental screening test (Korean-Ages and Stages Questionnaire [K-ASQ]), was a secondary outcome. The K-ASQ is performed annually from 1 to 6 years of age and consists of 5 domains. The association between general anesthesia and ADHD was estimated using a Cox hazard model, and its association with neurodevelopment was estimated using a generalized estimation equation, with control for multiple risk factors beyond 1 year after the index date. Results: The median age at the index date was 3.8 (95% confidence interval [CI], 1.7–5.8) years, and there were 57,625 (61.5%) men. During a mean follow-up period of 5 years, the incidence rate of ADHD was 42.6 and 27.7 per 10,000 person-years (PY) in the exposed and unexposed groups, respectively (absolute rate difference 14.9 [95% CI, 12.5–17.3] per 10,000 PY). Compared to the unexposed group, the exposed group had an increased risk of ADHD (adjusted hazard ratio, 1.41 [95% CI, 1.30–1.52]). In addition, a longer duration of anesthesia with ETI and more general anesthesia procedures with ETI were associated with greater risk of ADHD. General anesthesia with ETI was also associated with poorer results in the K-ASQ. Conclusion Administration of general anesthesia with ETI to children is associated with an increased risk of ADHD and poor results in a neurodevelopmental screening test.

PURPOSE: The in vitro study suggested that proline to serine polymorphism in codon 475 (C1423T) of the A Disintegrin and Metalloprotease with ThromboSpondin type 1 repeats-13 (ADAMTS-13) gene is related to reduced activity of ADAMTS- 13. In this study, the frequency of the Pro475Ser polymorphism in Koreans was studied and plasma ADAMTS-13 activity was measured to find out whether this polymorphism contributes to decreased ADAMTS-13 activity in Koreans. PATIENTS AND METHODS: The frequency of the C1423T allele of the ADAMTS13 gene was studied along with measuring plasma ADAMTS-13 activity in 250 healthy Korean individuals. RESULTS: The allele frequency of C1423T polymorphism was 4%, and the median activity of CT type was 107 (69-143)%, which was lower than in controls with the CC genotype [118 (48-197)%, (p=0.021)]. CONCLUSION: Therefore, the Pro475Ser polymorphism seems to be popular in the Korean population, and attenuates ADAMTS-13 plasma activity.
ADAM Proteins/blood/*genetics/metabolism ; Asian Continental Ancestry Group ; Fluorescence Resonance Energy Transfer ; Gene Frequency ; Genotype ; Humans ; *Polymorphism, Genetic

Leiomyoma and adenomyosis of the uterus are the most common gynecologic disorders in an enlarged uterus. The characteristic US and MR findings in differentiation between both lesions were prospectively evaluated in 30 patients. Of 30 patients, 15 were leiomyomas, 6 were adenomyosises, 8 were leiomyomas and adenomyosises, and 1 was a normal pregnancy, histologically. The total number of leiomyom nodules were 49 while adenomyosises were 14 (9 diffuse and 5 focal). Among 49 myomas nodules, 36 were correctly diagnosed by sonography. The characteristic US findings of uterine leiomyoma were well defined nodules (36), hypoechoic peripheral rim (16), and whorl-like internal echoes (13). Forty four of the 49 myoma nodules were correctly diagnosed by MRI. The characteristic MR findings of myoma were well defined nodules (43), peripheral low signal intensity rim on T1WI (13) and T2WI (9), and peripheral high signal intensity rim on T2WI (5). Among 14 adenomyosises, 9 were correctly diagnosed by sonography. The characteristic US findings of adenomyosis were diffuse uterine hypertrophy more than 5.5cm in AP diameter with endometrial displacement and no significant echo change in myometrium All 14 adenomyosis as were correctly diagnosed from MRI. On T2WI, adenomyosis appeared as ill defined localized or diffuse thickening of the junctional zone more than 1cm in thickness. It was our conclusion that to differentiate between leiomyoma and adenomyosis focused on should be the detection of existence of nodule in leiomyoma, the primary sign, not on the secondary indirect sign.
Adenomyosis* ; Animals ; Female ; Humans ; Hypertrophy ; Leiomyoma* ; Magnetic Resonance Imaging ; Mice ; Myoma ; Myometrium ; Pregnancy ; Prospective Studies ; Uterus

Although inverted papilloma (IP) of the nose and paranasal sinus is a benign neoplasm, it is associated with frequent recurrence and malignant transformation. Various surgical techniques have been employed for resection of this tumor. Transnasal endoscopic medial maxillectomy (TEMM) is an effective surgical management of IP originating from the maxillary sinus. It usually removes the inferior turbinate, lateral wall of the nasal cavity, and nasolacrimal duct, and may cause adverse effects such as atrophic rhinitis, empty nose syndrome, impairment of nasal physiological function, and epiphora. Recently, however, a modified TEMM, which preserves the inferior turbinate, lateral wall of the nasal cavity, and nasolacrimal duct has been introduced. We present two cases of IP successfully treated by the modified TEMM.
Endoscopy ; Lacrimal Apparatus Diseases ; Maxillary Sinus* ; Nasal Cavity ; Nasolacrimal Duct ; Nose ; Papilloma, Inverted* ; Recurrence ; Rhinitis, Atrophic ; Turbinates

OBJECTIVE: The aim of this study is to investigate the effects of cognitive training and cognitive trainer on cognitive function in persons with mild cognitive impairment (MCI). METHODS: A randomized controlled single blind trial with 2 treatment groups was designed and 40 participants were included in this study. They received cognitive training intervention by cognitive professional and non-professional. The cognitive training focused on memory strategies. This cognitive intervention consisted of 8 sessions training and once a week. The effect of program was examined in performance-based measures of cognitive abilities; memory, language, constructional praxis, attention, and working memory. The comparison of effect of trainer was examined by repeated measure analysis of variance. RESULTS: Thirty-six MCI completed the cognitive intervention and was assessed neurocognitive test on pre- and post-intervention. Attention, language inhibition and semantic language were significantly improved compared with baseline in total group. The memory (p=0.003) was significantly improved in Professional Program Group and attention (p=0.007) was significantly improved in Non-Professional Program Group (NPG). Distinctively, Korean version of Short form of Geriatric Depression Scale mean score in NPG was statistically improved from 4.24 to 3.29 (p=0.018) after intervention, but the comparison between groups was not significant. CONCLUSION: This study shows that the cognitive intervention program may improve on memory, attention and language in cognitive functions of MCI. But there is difference in improvement of the domains of cognitive abilities depending on the trainer.
Cognition ; Depression ; Humans ; Memory ; Memory, Short-Term ; Mild Cognitive Impairment ; Semantics

OBJECTIVE: To investigate the changes of causes, clinical features, and functional outcomes in childhood strokes. METHOD: This study included 152 patients, aged from 1 to 18 years, who were diagnosed with stroke and admitted to a tertiary hospital between January 2000 and April 2004. All medical records and neurologic images of the patients were reviewed. A parental questionnaire was used to investigate patients' functional outcomes. These results were compared with those of the previous study performed in the same hospital in 2001. RESULTS: The number of hemorrhagic stroke was 78 (51.3%) and that of ischemic stroke was 74 (48.7%). When compared to the previous study, the incidence of hemorrhagic stroke especially above the age of 10 years decreased and that of ischemic stroke below the age of 10 years increased. The causes of stroke were arteriovenous malformation (AVM, 42.8%), Moyamoya disease (37.5%), vasculitis (5.3%), cardiac disease (3.9%), hematologic disease (2.0%), and undetermined (8.5%). Common clinical features were headache (53.8%), vomiting (43.6%) and loss of consciousness (28.2%) in the hemorrhagic stroke, and hemiparesis (94.6%), headache (35.1%) and speech disorder (31.1%) in the ischemic stroke. 86.0% of the hemorrhagic and 64.8% of the ischemic stroke patients were categorized in the 'good' outcome group. CONCLUSION: The incidence of ischemic stroke increased to the similar level of hemorrhagic stroke. The most common causes were AVM in the hemorrhagic and Moyamoya disease in the ischemic stroke. Most of these patients showed good functional outcome, regardless of the causes of stroke.
Aged ; Arteriovenous Malformations ; Child ; Headache ; Heart Diseases ; Hematologic Diseases ; Humans ; Incidence ; Medical Records ; Moyamoya Disease ; Parents ; Paresis ; Surveys and Questionnaires ; Stroke ; Tertiary Care Centers ; Unconsciousness ; Vasculitis ; Vomiting